At cellular level, phosphoinositide-3-kinase (PI3K) signalling contributes to many important processes, such as cell cycle progression, cell growth, survival and migration and intracellular vesicular transport. The PI3K represents the family of lipid kinases that can be classified into three subfamilies according to structure and substrate specificity viz., class I, class II and class III (Liu et al., Nature review drug discovery, 2009, 8, 627; Courteny et al., J Clin Oncol, 2010, 28, 1075). The class I PI3Ks are the most extensively studied among lipid kinases, are heterodimeric proteins; each containing a smaller regulatory domain and a larger 110 kDa catalytic domain, which occur in four isoforms differentiated as p110α, p110β, p110γ, and p110δ (Walker et al., Mol. Cell 2000, 6, 909). Moreover, Isoform selective inhibitors capable of attenuating PI3K signalling should have significant therapeutic potential for the treatment of cancer, inflammatory (Barber et al., Nat. Med. 2005, 11, 933), cardiovascular diseases and autoimmune disorders. In cancer, evidence suggests that inhibition of the class 1A PI3 kinase p110α appear to be the most appropriate to target, as in number of cancer, p110α isoform is amplified and activated (Stephens et al., Curr. Opin. Pharmacol. 2005, 5, 357).
In the last decade, many small molecules have been discovered as PI3K isoform inhibitors and presenting the new opportunities as therapeutic agents. Some of the small molecules are presently in either phase I or II clinical trial against different type of cancers. Examples includes NVP-BEZ235 developed by Novartis, (Garcia-Echeverria et al., WO2006/122806A2), NVP-BGT226 developed by Novartis, (Kwang et al., Clin cancer res. 2011, 17(22), 7114), XL-147, XL-765 developed by Exelixis, (P. Wu et al., Eur. J. Med. Chem. 2011, 46, 5540), GDC0941 developed by Genentech, (Adrian et al., J. Med. Chem. 2008, 51, 5522), PKI-587 developed by Pfizer, (Mallon et al., Clin cancer res. 2011, 17(10), 3194), GSK1059615 developed by GSK, (Steven D. Knight et al., ACS Med. Chem. Lett. 2010, 1, 39), ZSTK474 developed by Zenyaku kogyo, (Yaguchi et al., J. Natl. Cancer inst. 2006, 98, 545; Kong et al., Cancer sci. 2007, 98, 1439; Gordon et al., J. Med. Chem. 2011, 54, 7105-7126; Gordon et al., WO2010/110686A1; Vladimir et al., WO2011/135520A1; Gordon et al., WO2010/110685A2; Venkatesan et al., WO2009/143317A1) etc. In spite of having many PI3K inhibitors in pre-clinical and different clinical trials, still there is need for the discovery of new PI3K inhibitors for the treatment of cancer.